Jin-Chen Yang1, Lillian Chi2, Sara Teichholtz2, Andrea Schneider3, Rawi Nanakul2, Ralph Nowacki4, Andreea Seritan5, Bruce Reed6, Charles DeCarli6, Vicente J Iragui4, Marta Kutas7, Paul J Hagerman8, Randi J Hagerman3, John M Olichney9. 1. University of California Davis, Center for Mind and Brain, Davis, CA 95618-5412, USA; University of California Davis, Department of Neurology, School of Medicine, Sacramento, CA 95618-5412, USA. Electronic address: jchyang@ucdavis.edu. 2. University of California Davis, Center for Mind and Brain, Davis, CA 95618-5412, USA; University of California Davis, Department of Neurology, School of Medicine, Sacramento, CA 95618-5412, USA. 3. University of California Davis, M.I.N.D. Institute, School of Medicine, Sacramento, CA, USA; University of California Davis, Department of Pediatrics, School of Medicine, Sacramento, CA, USA. 4. University of California San Diego, Department of Neurosciences, San Diego, CA, USA; VA San Diego Healthcare System, San Diego, CA, USA. 5. University of California Davis, Department of Psychiatry and Behavioral Sciences, School of Medicine, Sacramento, CA, USA. 6. University of California Davis, Department of Neurology, School of Medicine, Sacramento, CA 95618-5412, USA. 7. University of California San Diego, Department of Cognitive Sciences, San Diego, CA, USA. 8. University of California Davis, Department of Biochemistry and Molecular Medicine, Davis, CA, USA. 9. University of California Davis, Center for Mind and Brain, Davis, CA 95618-5412, USA; University of California Davis, Department of Neurology, School of Medicine, Sacramento, CA 95618-5412, USA. Electronic address: jmolichney@ucdavis.edu.
Abstract
BACKGROUND: Fragile X-associated tremor/ataxia syndrome (FXTAS), a neurodegenerative disorder caused by FMR1 gene premutations, typically associated with frontal-subcortical type cognitive impairments. High prevalence (~50%) of superimposed Alzheimer׳s pathology has been reported in FMR1 premutation carriers, and standardized neuropsychological tests have not yielded any robust discriminators between FXTAS and Alzheimer׳s disease (AD) dementia. The similarities/differences in memory processes between FXTAS and early AD remain underexplored. METHODS: 32-channel event-related potentials (ERPs) were obtained from a semantic judgment task in which semantically congruous (50%) and incongruous pairs repeat pseudorandomly. The N400 and late positive component (LPC) of 25 FXTAS patients (M(age)=71.2, MMSE=26.6) were compared to a matched group of 25 patients with MCI or early AD (1 mild AD dementia, 24 amnestic MCI, of whom 18 later converted to AD; M(age)=73.4, MMSE=26.4), and 25 healthy elderly. RESULTS: Both patient groups showed similar reductions in the N400 repetition effect and N400 congruity effect amplitudes, compared to controls, reflecting abnormal semantic priming and repetition priming. The MCI/AD group, however, had significantly smaller LPC word repetition effects and poorer learning and memory on the CVLT than FXTAS. The LPC and N400 repetition effects both correlated with verbal memory across all subjects, but only N400 correlated with memory in FXTAS. CONCLUSION: FXTAS patients show relative sparing of the LPC repetition effect, and less disruption of explicit memory than prodromal/early AD. N400 abnormalities in FXTAS appear to account for much of their mild impairments in verbal learning and memory.
BACKGROUND:Fragile X-associated tremor/ataxia syndrome (FXTAS), a neurodegenerative disorder caused by FMR1 gene premutations, typically associated with frontal-subcortical type cognitive impairments. High prevalence (~50%) of superimposed Alzheimer׳s pathology has been reported in FMR1 premutation carriers, and standardized neuropsychological tests have not yielded any robust discriminators between FXTAS and Alzheimer׳s disease (AD) dementia. The similarities/differences in memory processes between FXTAS and early AD remain underexplored. METHODS: 32-channel event-related potentials (ERPs) were obtained from a semantic judgment task in which semantically congruous (50%) and incongruous pairs repeat pseudorandomly. The N400 and late positive component (LPC) of 25 FXTAS patients (M(age)=71.2, MMSE=26.6) were compared to a matched group of 25 patients with MCI or early AD (1 mild AD dementia, 24 amnestic MCI, of whom 18 later converted to AD; M(age)=73.4, MMSE=26.4), and 25 healthy elderly. RESULTS: Both patient groups showed similar reductions in the N400 repetition effect and N400 congruity effect amplitudes, compared to controls, reflecting abnormal semantic priming and repetition priming. The MCI/AD group, however, had significantly smaller LPCword repetition effects and poorer learning and memory on the CVLT than FXTAS. The LPC and N400 repetition effects both correlated with verbal memory across all subjects, but only N400 correlated with memory in FXTAS. CONCLUSION: FXTAS patients show relative sparing of the LPC repetition effect, and less disruption of explicit memory than prodromal/early AD. N400 abnormalities in FXTAS appear to account for much of their mild impairments in verbal learning and memory.
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